دورية أكاديمية

Cellular Epigenetic Modifications of Neural Stem Cell Differentiation

التفاصيل البيبلوغرافية
العنوان: Cellular Epigenetic Modifications of Neural Stem Cell Differentiation
المؤلفون: Rabindra P. Singh, Kevin Shiue, Dominic Schomberg, Feng C. Zhou Ph.D.
المصدر: Cell Transplantation, Vol 18 (2009)
بيانات النشر: SAGE Publishing, 2009.
سنة النشر: 2009
المجموعة: LCC:Medicine
مصطلحات موضوعية: Medicine
الوصف: Emerging information indicates that epigenetic modification (i.e., histone code and DNA methylation) may be integral to the maintenance and differentiation of neural stem cells (NSCs), but their actual involvement has not yet been illustrated. In this study, we demonstrated the dynamic nature of epigenetic marks during the differentiation of quiescent adult rat NSCs in neurospheres. A subpopulation of OCT4 + NSCs in the neurosphere contained histone marks, trimethylated histone 3 on lysine 27 (3me-H3K27), 2me-H3K4, and acetylated H4 (Ac-H4). A major decrease of these marks was found prior to or during differentiation, and was further diminished or reprogrammed in diverse subpopulations of migrated NSCs expressing nestin or β-III-tubulin. The DNA methylation mark 5-methyl-cytosine (5-MeC), and DNA methyltransferase (DNMT) 1 and 3a expression also correlated to the state of differentiation; they were highly present in undifferentiated NSCs but downregulated in migrated populations. In contrast, DNA methyl-CpG-binding protein (MBD1) was low in undifferentiated NSCs in neurospheres, but highly appeared in differentiating NSCs. Furthermore, we found an outward translocation of DNA methylation marker 5-MeC, DNMT1, DNMT3a, and MBD1 in NSCs as differentiation began and proceeded; 5-MeC from homogeneous nucleus to peripheral nucleus, and DMNT1a and 3a from nuclear to cytoplasm, indicating chromatin remodeling. Treatment with DNA methylation inhibitor, 5-aza-cytidine, altered DNA methylation and disrupted migration as indicated by a reduction of migrated neurons and differentiation. These results indicate that chromatin is dynamically remodeled when NSCs transform from the quiescent state to active growth, and that DNA methylation modification is essential for neural stem cell differentiation.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 0963-6897
1555-3892
Relation: https://doaj.org/toc/0963-6897; https://doaj.org/toc/1555-3892
DOI: 10.3727/096368909X12483162197204
URL الوصول: https://doaj.org/article/310026dbe03c4ae1816fe8995d5e4944
رقم الأكسشن: edsdoj.310026dbe03c4ae1816fe8995d5e4944
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:09636897
15553892
DOI:10.3727/096368909X12483162197204